The proposed research is designed to analyze the mechanism by which helper T lymphocytes are inactivated following exposure to suppressor cells. A model for the inactivation of helper cells by suppressor cells is presented, and the experiments are designed to test the model. The model proposes that suppressor and helper cells come into proximity on the surface of an antigen presenting macrophage. When the suppressor cell is triggered by interaction with antigen and self determinants on the macrophage surface, a factor is released whose target is the helper cell also attached to the macrophage surface via antigen and self receptors. The following questions concerning the model will be asked: 1) What are the antigen, macrophage, specificity, kinetic, and genetic requirements for helper cell inactivation? 2) What is the duration of helper cell inactivation? 3) Do suppressor cells inactivate subsets of T helpers? 4) Is there a requirement for an inducing signal for suppressor cell function? 5) Why is their a differential sensitivity of Ly 1 helpers and inducers of feedback suppression to suppressor T cell activity. The long term goal of this research is to understand the cell biology of helper cell inactivation.